Escherichia coli-Derived Outer Membrane Vesicles Deliver Galactose-1-Phosphate Uridyltransferase and Yield Partial Protection against Actinobacillus pleuropneumoniae in Mice

J Microbiol Biotechnol. 2018 Dec 28;28(12):2095-2105. doi: 10.4014/jmb.1809.09004.

Abstract

In our previous studies, we have identified several in vivo-induced antigens and evaluated their potential as subunit vaccine candidates in a murine model, in which the recombinant protein GalT showed the most potent immunogenicity and immunoprotective efficacy against Actinobacillus pleuropneumoniae. To exploit a more efficient way of delivering GalT proteins, in this study, we employed the widely studied E. coli outer membrane vesicles (OMVs) as a platform to deliver GalT protein and performed the vaccine trial using the recombinant GalT-OMVs in the murine model. Results revealed that GalT-OMVs could elicit a highly-specific, IgG antibody titer that was comparable with the adjuvant GalT group. Significantly higher lymphocyte proliferation and cytokines secretion levels were observed in the GalT-OMVs group. 87.5% and 50% of mice were protected from a lethal dose challenge using A. pleuropneumoniae in active or passive immunization, respectively. Histopathologic and immunohistochemical analyses showed remarkably reduced pathological changes and infiltration of neutrophils in the lungs of mice immunized with GalT-OMVs after the challenge. Taken together, these findings confirm that OMVs can be used as a platform to deliver GalT protein and enhance its immunogenicity to induce both humoral and cellular immune responses in mice.

Keywords: Actinobacillus pleuropneumoniae,; GalT protein; OMVs; immunoprotective efficacy.

MeSH terms

  • Actinobacillus Infections / immunology*
  • Actinobacillus Infections / pathology
  • Actinobacillus Infections / prevention & control*
  • Actinobacillus pleuropneumoniae / drug effects*
  • Actinobacillus pleuropneumoniae / immunology
  • Actinobacillus pleuropneumoniae / pathogenicity
  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Bacterial
  • Bacterial Outer Membrane Proteins / immunology
  • Bacterial Vaccines / genetics
  • Bacterial Vaccines / immunology*
  • Cell Proliferation
  • Cytokines / metabolism
  • Disease Models, Animal
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Female
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunization*
  • Immunoglobulin G
  • Lethal Dose 50
  • Lung / pathology
  • Lymphocytes
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / pathology
  • Protein Engineering
  • Protein Transport / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • UTP-Hexose-1-Phosphate Uridylyltransferase / genetics
  • UTP-Hexose-1-Phosphate Uridylyltransferase / immunology*
  • UTP-Hexose-1-Phosphate Uridylyltransferase / metabolism
  • Vaccination

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Cytokines
  • Immunoglobulin G
  • Recombinant Fusion Proteins
  • UTP-Hexose-1-Phosphate Uridylyltransferase